[The effect of hypolipemic treatment on the pharmacokinetics of propranolol].
The influence of elevated concentration of lipids in blood on the concentration of drugs in organism was observed in 1976. The following experiments have revealed that pharmacokinetics of lipophilic drugs in hyperlipidemia is altered. The purpose of this paper was to evaluate the effect of hypolipemic treatment on the propranolol pharmacokinetics, to take into account phenotype of hydroxylation and type of primary hyperlipidemia. The study was carried out on 37 patients (34 patients EM and 3 patients PM) with hypercholesterolemia, hypertriglyceridemia and mixed form of hyperlipidemia. Duration of hypolipemic therapy was 30 days. Pharmacokinetic studies were carried out twice i.e. at the onset of the study and following a 30-day period of hypolipemic treatment. Propranolol was given orally as a single dose 80 mg. Blood serum was sampled during administration. HPLC method was used to determine blood serum concentration of propranolol. The one-compartment model was applied for calculation of pharmacokinetic parameters. The obtained results have disclosed that hypolipemic therapy altered pharmacokinetic parameters of propranolol. Intensity and course of these changes depend on the type of hyperlipidemia. The most pronounced changes were observed in patients EM with hypertriglyceridemia. Lowering of propranolol concentration in blood, elevated penetration into tissues and accelerated elimination were revealed (Fig. 3, 4). Similar changes, but lesser intensity were observed in patients with mixed form of hyperlipidemia (Fig 5, 6). Alteration of pharmacokinetic parameters of propranolol in hypercholesterolemic patients were slight and contrasting the patients with hypertriglyceridemia and mixed form of hyperlipidemia. The lowering of cholesterol concentration in blood has slight influence on normalization of propranolol kinetics (Fig 1, 2). In patients with phenotype PM pharmacokinetic parameters of propranolol were changed, under used treatment too. Due to the limited number of patients, conclusions should be carefully drawn. The actual results have disclosed a decrease in lipids concentration, mainly triglycerides, which causes changes in pharmacokinetics of propranolol in patients with phenotype PM as well.
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Z Katedry Farmakologii i Toksykologii Pomorskiej Akademii Medycznej w Szczecinie, Szczecin.
D000284:Administration, Oral; D000924:Anticholesteremic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D001629:Bezafibrate / Q000494:pharmacology / Q000627:therapeutic use*; D002851:Chromatography, High Pressure Liquid; D004347:Drug Interactions; D005260:Female; D006801:Humans; D006900:Hydroxylation; D006937:Hypercholesterolemia / Q000188:drug therapy; D006949:Hyperlipidemias / Q000188:drug therapy*; D015228:Hypertriglyceridemia / Q000188:drug therapy; D000960:Hypolipidemic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D008148:Lovastatin / Q000494:pharmacology / Q000627:therapeutic use*; D008297:Male; D010641:Phenotype; D011433:Propranolol / Q000008:administration & dosage / Q000097:blood*; D014280:Triglycerides / Q000097:blood
D000924:Anticholesteremic Agents; D000960:Hypolipidemic Agents; D014280:Triglycerides; D008148:Lovastatin; D011433:Propranolol; D001629:Bezafibrate
Wpływ leczenia hipolipemicznego na farmakokinetyke propranololu.